蛭田 勇樹 (ヒルタ ユウキ)

Hiruta, Yuki

写真a

所属(所属キャンパス)

理工学部 応用化学科 (矢上)

職名

専任講師

学位 【 表示 / 非表示

  • 博士(工学), 慶應義塾大学理工学研究科総合デザイン工学専攻, 論文

 

論文 【 表示 / 非表示

  • Long-term single cell bioluminescence imaging with C-3 position protected coelenterazine analogues

    Mizui Y., Eguchi M., Tanaka M., Ikeda Y., Yoshimura H., Ozawa T., Citterio D., Hiruta Y.

    Organic and Biomolecular Chemistry (Organic and Biomolecular Chemistry)  19 ( 3 ) 579 - 586 2021年01月

    ISSN  14770520

     概要を見る

    © The Royal Society of Chemistry 2020. Bioluminescence is a powerful imaging modality for monitoring biological phenomena bothin vitroandin vivo. Bioluminescence imagin (BLI) is becoming a seamless imaging technology covering the range from cells to organs of small animals. Long-term imaging at the single cell level would lead to a true understanding of the dynamics of life phenomena. This work presents a long-term single cell bioluminescence imaging technology accomplished with C-3 position protected furimazines (FMZs), a CTZ analogues, which generate intense blue emission when paired with a highly stable engineered luciferase, Nanoluc. Four types of FMZs protected at the C-3 position have been synthesized. The type and steric bulkiness of the protection group strongly contributed to storage stability and the kinetics of the bioluminescence reactions of the analogues in human living cells. In particular, two developed FMZ analogues resulted in significantly longer bioluminescence emission with higher S/N ratio than FMZ at single cell level. Long-term bioluminescence single cell imaging technology with the developed FMZ analogues will lead to seamless imaging in the range from cells to organs of small animals.

  • Anionic fluorophore-assisted fabrication of gold microstructures inside a hydrogel by multi-photon photoreduction

    Machida Manan, Shen Weilu, Onoe Hiroaki, Hiruta Yuki, Heisterkamp Alexander, Mazur Eric, Terakawa Mitsuhiro

    OPTICAL MATERIALS EXPRESS 11 ( 1 ) 48 - 58 2021年01月

    ISSN  2159-3930

  • Near-infrared pH responsive heptamethine cyanine platforms: Modulating the proton acceptor

    Kurutos A., Shindo Y., Hiruta Y., Oka K., Citterio D.

    Dyes and Pigments (Dyes and Pigments)  181 2020年10月

    ISSN  01437208

     概要を見る

    © 2020 Elsevier Ltd In this report, we wish to present the rational design, synthesis, and study of optical characteristics of near-infrared (NIR) molecular probes emitting over 800 nm. The title pH sensing platforms consist of a piperazine moiety serving as a hydronium ion receptor, coupled with a rigidified symmetric heptamethine backbone. The spectrally fine-tuned response of the fluorophores was studied in both organic solvents and aqueous buffer solutions, employing combined UV–Vis and steady state fluorimetric techniques. In parallel, computational approach and optical spectroscopy were employed aiming to ascribe the origin of spectral behavior of the amino-substituted heptamethines. Herein, we also investigated the halochromic effect of the differently substituted piperazines on the spectral properties of the NIR cyanine dyes. Under acidic conditions, the protonation of the piperazine moiety promoted a gradual bathochromic shift in the absorption spectra. The Δλ between the neutral and the protonated forms are indirectly related to the modifications applied to the proton acceptor. The calculated pKa values (5.13–7.06) were found to be dependent on the dye chemical structure. A good linear correlation was established between the pKa of the newly synthesized dyes and that of the reported piperazine moieties. This aspect allows the future expansion of the current facile strategy since sensing chromophores with predicted pH response could readily be designed based on pKa databases for substituted piperazine derivatives. A detailed literature study along with NMR and computational methods were found to be in agreement with our assumption, that both nitrogen atoms of the 1,4-disubstituted amine are involved in the sensing process. The covered pKa range allows us to recommend the title fluorophores as promising potential candidates for qualitative analysis of biological samples. A cytotoxicity study by the MTT assay showed that the NIR dyes are safe and applicable for bioanalytical purposes at dye concentrations up to 10 μM. Fluorescence imaging and cellular applications, including staining and visualization of HeLa cervical cancer cells was successfully demonstrated.

  • All-printed semiquantitative paper-based analytical devices relying on QR code array readout

    Katoh A., Maejima K., Hiruta Y., Citterio D.

    The Analyst (The Analyst)  145 ( 18 ) 6071 - 6078 2020年09月

    ISSN  0003-2654

     概要を見る

    The wide spread of smartphones and QR codes for various end-user applications has had an impact beyond traditional fields of use, recently also reaching point-of-care testing (POCT). This work presents the integration of QR code recognition into paper-based analytical devices (PADs) with "distance-based" colorimetric signalling, resulting in semiquantitative readout fully relying on straightforward barcode reader solutions. PADs consist of an array of QR codes arranged in series inside a paperfluidic channel. A mask dye concept has been developed, which enables utilisation of colour changing indicators by initially hiding QR codes. The colour change of the indicator induced by the presence of an analyte of interest results in gradual unmasking of QR codes, which become recognisable by the smartphone barcode reader app. To reproducibly fabricate devices, all fabrication steps were performed by commercial desktop solid ink and inkjet printing. The QR code masking function was optimised by controlling the amount of printed mask dye through adjusting the opacity of printing patterns during the inkjet deposition process. For proof-of-concept, a model assay in the form of colorimetric copper ion (Cu2+) detection in the concentration range of 0.4 mM to 3.2 mM was evaluated. Consistent results independent of the smartphone model and environmental light condition were achieved with a free barcode reader app. To the best of our knowledge, this work is the first demonstration of a semiquantitative assay approach fully relying on QR code readout without digital colour analysis, customised app or hardware modification.

  • Text-Displaying Semiquantitative Competitive Lateral Flow Immunoassay Relying on Inkjet-Printed Patterns

    Misawa K., Yamamoto T., Hiruta Y., Yamazaki H., Citterio D.

    ACS Sensors (ACS Sensors)  5 ( 7 ) 2076 - 2085 2020年07月

    ISSN  2379-3694

     概要を見る

    Copyright © 2020 American Chemical Society. This work describes a colorimetric signaling approach for competitive lateral flow immunoassays (LFIAs) enabling sensitive and semiquantitative direct visual result readout in the form of "text", demonstrated on the example of 8-hydroxy-2′-deoxyguanosine (8-OHdG) detection. The distinctive feature of the developed text-displaying LFIA (TD-LFIA) is the test zone system consisting of a combination of two types of inkjet-deposited capture molecules referred to as "mask antigen"and "text antibody", allowing for sensitive turn-on signaling as opposed to the inverse response of conventional competitive LFIAs. The user operation is limited to sample application, followed by direct reading of assay results written in text after approximately 10 min. TD-LFIAs enabled the visual detection of 8-OHdG at concentrations down to 3 ng/mL, which is a 2-3 orders of magnitude lower visual detection limit than that achieved with the corresponding conventional design and is comparable to the existing LFIAs relying on external signal readout equipment. Highly reproducible observer-independent assay performance was confirmed, and the result interpretation is not influenced by sample color and readout timing. Making use of customizable threshold settings for text appearance, a device for semiquantitative assays was developed and successfully applied to the detection of 8-OHdG at four concentration levels (trace, low, medium, and high) in 54 human urine samples within the clinically relevant concentration range. The sensitive and intuitive signaling method of the developed system offers great potential for an alternative competitive LFIA platform suitable for real-world point-of-care testing applications.

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

研究発表 【 表示 / 非表示

  • 近赤外蛍光マグネシウムイオンプローブの開発と マルチカラー細胞イメージングへの応用

    蛭田勇樹

    日本分析化学会第68年会, 2019年09月, 口頭(一般)

  • pH-response tunable mixed-charged polymers for reversible adsorption and desorption of proteins

    ACS Fall 2019 National Meeting & Exposition, 2019年08月, 口頭(一般)

  • Development of temperature-responsive polymer materials for cancer therapy and imaging

    The 2019 Controlled Release Society Annual Meeting & Exposition, 2019年07月, ポスター(一般)

  • pH-Responsive mixed-charge polymer for weak acidic tumorous environment selective cellular uptake

    蛭田勇樹

    第68回高分子学会年次大会, 2019年05月, 口頭(一般)

  • 耐アルカリ性を持つ炭酸カルシウム多孔質粒子を母体とするHPLC充填剤の開発

    蛭田勇樹

    日本化学会第99春季年会, 2019年03月, 口頭(一般)

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競争的資金等の研究課題 【 表示 / 非表示

  • 時空間トランススケールイメージングを可能にする高分子ケージドルシフェリンの開発

    2019年04月
    -
    2021年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 蛭田 勇樹, 新学術領域研究(研究課題提案型), 補助金,  代表

  • 腫瘍への自己集積増幅機能を持つセラノスティクスナノプラットフォームの創製

    2019年04月
    -
    2021年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 蛭田 勇樹, 若手研究, 補助金,  代表

  • 血中抗体医薬品のPOC分析を可能にするマイクロ流体糸基板センサー

    2018年04月
    -
    2021年03月

    チッテリオ ダニエル, 補助金,  分担

  • 論理的高分子設計によるデュアルpH応答型ドラッグデリバリーキャリアの創製

    2015年04月
    -
    2017年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 蛭田 勇樹, 若手研究(B), 補助金,  代表

     研究概要を見る

    局所加温による温度変化、細胞内小胞の低pHに注目した2段階温度、pH応答性ブロックポリマーを設計し、抗がん剤のドキソルビシンを内包させてミセル化し、がん細胞選択的な取り込み、および細胞取り込み後の薬物放出が可能なドラッグキャリアを創製した。このポリマーミセルは、体温よりも少し高い温度で相転移することで、細胞取り込み量が増加した。細胞毒性への温度の影響を調べたところ、42°Cでは37°Cに比べて有意な細胞毒性を示した。温度変化による細胞取り込みコントロールと細胞内小胞の酸性環境を認識しドキソルビシンを効率良く放出する2段階の応答機能を持ち、がん細胞に対して有効な作用を示した。

  • LAT1選択的蛍光ポリマープローブの創製とがん可視化への応用

    2015年01月
    -
    2015年12月

    代表

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受賞 【 表示 / 非表示

  • 日本分析化学会奨励賞

    2020年08月, 公益社団法人日本分析化学会, 精密分子設計に基づくバイオイメージングプローブの開発と応用

    受賞区分: 国内学会・会議・シンポジウム等の賞

  • 高分子研究奨励賞

    Development of stimuli-responsive polymer materials for application to medical analysis, 2020年05月, 公益社団法人高分子学会, 医療分析への応用を志向した刺激応答性高分子材料の開発

    受賞区分: 国内学会・会議・シンポジウム等の賞

  • 日本化学会第99春季年会 優秀講演賞(学術)

    2019年04月, 公益財団法人 日本化学会

    受賞区分: 国内学会・会議・シンポジウム等の賞

  • 平成29年度物理系薬学部会奨励賞

    2017年03月, 日本薬学会 物理系薬学部会, 診断技術への応用を目指したスマートポリマープローブの精密設計

  • 平成27年度慶應義塾大学薬学部長賞(研究)

    2016年03月

    受賞区分: 塾内表彰等

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担当授業科目 【 表示 / 非表示

  • 応用化学実験A

    2021年度

  • 機能物質概論

    2021年度

  • 総合デザイン工学課題研究

    2021年度

  • 総合デザイン工学特別研究第2

    2021年度

  • 総合デザイン工学特別研究第1

    2021年度

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所属学協会 【 表示 / 非表示

  • クロマトグラフィー科学会会員, 

    2016年01月
    -
    継続中
  • 高分子学会会員, 

    2016年01月
    -
    継続中
  • 日本DDS学会会員, 

    2014年04月
    -
    継続中
  • 日本薬学会会員, 

    2014年01月
    -
    継続中
  • 日本化学会会員, 

    2010年01月
    -
    継続中

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委員歴 【 表示 / 非表示

  • 2019年12月
    -
    継続中

    化学グランプリ・オリンピック委員会 グランプリ小委員会 委員, 公益社団法人日本化学会

  • 2018年04月
    -
    継続中

    代議員, 日本分析化学会

  • 2017年01月
    -
    2018年12月

    関東支部幹事, 日本分析化学会